Shedding and regeneration of the endometrium is critical for embryo implantation. Disordered shedding (endometriosis, adenomyosis) and/or regeneration (Asherman’s Syndrome) is associated with debilitating menstrual disorders. Endometrial stem/progenitor cells, likely responsible for endometrial regeneration, are SUSD2+ mesenchymal stem cells (eMSCs) and N-cadherin+ (NCAD) epithelial progenitors (eEPC). NCAD+ eEPC form gland-like structures in organoid cultures, self-renew and are located in the bases of endometrial glands. SUSD2+ cells are perivascular cells in the endometrium. SUSD2+ eMSC and NCAD+ eEPC are shed during menstruation in women with/without endometriosis (unpublished). Our aim was to determine if there are biological variations in endometrial stem/progenitor cell concentrations and clonogenicity in menstrual fluid between menstrual cycles in normal women and between women.
Menstrual fluid (day 2) was collected from healthy women (not on hormones; regular cycles) in a menstrual cup. Endometrial cells were dissociated with enzymes, leukocytes depleted by CD45 magnetic beads and red blood cells by hypotonic lysis. The %SUSD2+ and %NCAD+ cells were determined by flow cytometry and clonogenicity by colony forming assays (cell seeding, 50/cm2).
Menstrual fluid was collected from 3 women over 3 cycles. SUSD2+ cells were present in all menstrual fluids (1.0-7.1% of CD45- cells; median 5.4%). NCAD+ cells were detected in 5 of 7 samples (0-3.0% of CD45- cells; median 0.6%) with no variation between cycles or participants (p=0.4). The clonogenicity of CD45-endometrial cells (3.9% - 17.8%) was also similar across cycles and between women.
In this pilot study, there was a lower frequency of NCAD+ cells compared to SUSD2+ cells in menstrual fluid as expected from their location. Further samples are required to fully determine the variability of endometrial stem/progenitor cells shed between women and between cycles of individual women. Quantification of endometrial stem/progenitor cells in menstrual blood may be a simple, non-invasive method for prognosis of fertility and endometrial disorders.